Immunoconjugates that neutralize HIV virions kill T cells infected with diverse strains of HIV-1.
Two murine monoclonal antibodies, G3.519, recognizing the CD4-binding region, and BAT123, a variable region of gp120 of human immunodeficiency virus, were chemically coupled to pokeweed antiviral protein isolated from seeds (PAP-S). The immunoconjugates were purified by Sephacryl S-200 gel filtration and Mono S ion exchange chromatography. Immunoconjugate G3.519-PAP-S specifically killed human T cells, H9, infected with three diverse HIV-1 strains, HTLV-IIIB, -IIIMN, and -IIIRF. Inhibition of thymidine incorporation by the immunoconjugate was concentration-dependent, with the ID50 ranging from 1.4 x 10(-10) M to 1.7 x 10(-9) M. Immunoconjugate BAT123-PAP-S was effective in killing H9 cells infected with HTLV-IIIB (ID50 = 4.3 x 10(-11) M) and -IIIMN (ID50 = 4.7 x 10(-10) M), but not -IIIRF. Both immunoconjugates did not inhibit thymidine incorporation in uninfected H9 cells up to a concentration of 5.3 x 10(-8) M, and their cytotoxic activities could be competitively blocked by the respective unconjugated antibodies. The immunoconjugates retained the ability to neutralize HIV virions to infect T cells and to prevent the syncytium formation. These in vitro studies suggest that the use of immunoconjugates capable of killing HIV-infected T cells and neutralizing virus may provide an alternative treatment for HIV-infected persons.
Kim
Y W
YW
Tanox Biosystems, Inc., Houston, TX 77025.
Fung
M S
MS
Sun
N C
NC
Sun
C R
CR
Chang
N T
NT
Chang
T W
TW
D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D002470:Cell Survival; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D000922:Immunotoxins / Q000276:immunology* / Q000302:isolation & purification; D066298:In Vitro Techniques; D009699:N-Glycosyl Hydrolases; D009500:Neutralization Tests; D010940:Plant Proteins / Q000008:administration & dosage; D054789:Ribosome Inactivating Proteins, Type 1; D013045:Species Specificity; D013601:T-Lymphocytes / Q000166:cytology / Q000382:microbiology*
D000911:Antibodies, Monoclonal; D015699:HIV Envelope Protein gp120; D000922:Immunotoxins; D010940:Plant Proteins; D054789:Ribosome Inactivating Proteins, Type 1; D009699:N-Glycosyl Hydrolases; C024275:pokeweed antiviral protein